Comparison of an Increased Dosage Regimen of Rabeprazole Versus a Concomitant Dosage Regimen of Famotidine with Rabeprazole for Nocturnal Gastric Acid Inhibition in Relation to Cytochrome P450 2C19 Genotypes
Comparison of an Increased Dosage Regimen of Rabeprazole Versus a Concomitant Dosage Regimen of Famotidine with Rabeprazole for Nocturnal Gastric Acid Inhibition in Relation to Cytochrome P450 2C19 Genotypes
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DOI：
10.1016/j.clpt.2004.10.010
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发表时间：
2005-04
影响因子：
6.7
通讯作者：
M. Sugimoto;T. Furuta;N. Shirai;A. Nakamura;M. Kajimura;A. Hishida;K. Ohashi;T. Ishizaki
中科院分区：
文献类型：
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作者：
M. Sugimoto;T. Furuta;N. Shirai;A. Nakamura;M. Kajimura;A. Hishida;K. Ohashi;T. Ishizaki
背景和目的组胺2受体拮抗剂与质子泵抑制剂（PPI）的联合给药方案可有效降低夜间酸突破的发生率，这是单独使用PPI治疗酸相关疾病时遇到的问题之一。我们比较了雷贝拉唑与法莫替丁的伴随剂量方案的雷贝拉唑与法莫替丁，相对于细胞色素P450（CYP 19）2C 19基因型状态，对夜间酸抑制的有效性增加剂量方案。分别于睡前（晚上10点）服用雷贝拉唑20 mg、40 mg、20 mg+法莫替丁20 mg，共8天。结果20 mg、40 mg雷贝拉唑组和联合用药组夜间胃内pH值低于4.0的中位百分比时间和范围为78.8%（47.5%-98.0%）、45.3%（29.0%-52.2%）和15.5%（0.0%-40.8%）; 51.0%（7.0%-91.6%），41.3%杂合子EM分别为33.0%-59.0%和18.5%（8.4%-31.9%）; PM分别为4.5%（2.0%-31.2%）、9.5%（0.0%-31.1%）和9.3%（0.0%-14.7%）。虽然当单独给予雷贝拉唑时，观察到不同CYP 2C 19基因型之间的酸抑制存在显著差异，（20 mg雷贝拉唑P= 0.016，40 mg雷贝拉唑P = 0.023），当同时给予法莫替丁时，未观察到这种差异（P= .206）结论法莫替丁联合雷贝拉唑治疗纯合子和杂合子型EM患者的夜间抑酸效果优于单用雷贝拉唑。雷贝拉唑的给药方案。对于标准PPI治疗难治的夜间酸突破患者（可能为CYP 2C 19 EMs），该伴随治疗可作为补救方案。Clinical Pharmacology & Therapeutics（2005）77，302-311; doi：10.1016/j.clpt.2004.10.010
Background and objectiveA concomitant dosage regimen of a histamine 2 receptor antagonist with a proton pump inhibitor (PPI) effectively decreases the incidence of nocturnal acid breakthrough, which is one of the problems encountered when acid‐related diseases are treated with a PPI alone. We compared the effectiveness of an increased dosage regimen of rabeprazole with that of a concomitant dosage regimen of rabeprazole with famotidine, relative to cytochrome P450 (CYP) 2C19 genotype status, on nocturnal acid inhibition.MethodsFifteenHelicobacter pylori–negative volunteers, consisting of 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took 20 mg rabeprazole, 40 mg rabeprazole, and 20 mg rabeprazole plus 20 mg famotidine at bedtime (at 10PM) for 8 days. The subjects then underwent 24‐hour intragastric pH monitoring on day 8.ResultsFor the 20‐mg rabeprazole, 40‐mg rabeprazole, and concomitant dosage regimens, the median percent times and ranges when nocturnal intragastric pH values were lower than 4.0 were 78.8% (47.5%‐98.0%), 45.3% (29.0%‐52.2%), and 15.5% (0.0%‐40.8%), respectively, for homozygous EMs; 51.0% (7.0%‐91.6%), 41.3% (33.0%‐59.0%), and 18.5% (8.4%‐31.9%), respectively, for heterozygous EMs; and 4.5% (2.0%‐31.2%), 9.5% (0.0%‐31.1%), and 9.3% (0.0%‐14.7%), respectively, for PMs. Although significant differences in acid inhibition between the different CYP2C19 genotypes were observed when rabeprazole alone was given (P= .016 for 20 mg rabeprazole andP= .023 for 40 mg rabeprazole), such differences were not observed when famotidine was concomitantly given (P= .206).ConclusionsThe combination regimen of famotidine plus rabeprazole is more effective for nocturnal acid inhibition in homozygous and heterozygous EMs than the increased dosage regimen of rabeprazole. This concomitant therapy could be a rescue regimen for patients with nocturnal acid breakthrough refractory to a standard PPI therapy who are likely to be CYP2C19 EMs.Clinical Pharmacology & Therapeutics(2005)77, 302–311; doi: 10.1016/j.clpt.2004.10.010